Looking back at the ISMP Medication Safety Alert! newsletters over the past few years, many topics of great importance to patient safety have repeatedly surfaced, but perhaps none as ominous as the ongoing drug shortage crisis and unsafe sterile compounding and preparation of pharmaceutical products. Both issues recently resurfaced in our March 22, 2012 newsletter, as we discussed the results of our survey on drug storage, stability, compatibility, and beyond use dating of pharmaceuticals.

The survey uncovered unnecessary waste of drugs during severe shortages when complying with the manufacturer’s compatibility, stability, and beyond use dating instructions (if available)—as the Centers for Medicare & Medicaid Services (CMS) currently requires—even if there is newer evidence-based information in nationally recognized compendia such as Trissel’s 2 Clinical Pharmaceutics Database or Handbook on Injectable Drugs that would safely conserve these drugs. The survey also confirmed that products in short supply have been compounded in hospital, retail, and specialty pharmacies, which has led to serious infection outbreaks due to sterility breeches and other preparation errors. Pharmacists also reported that nurses have been asked to prepare IV admixtures in patient areas due to short stability and beyond use dating in the manufacturer’s directions when more liberal stability and beyond use dating in compendia would allow pharmacy preparation.

As we reported last month, CMS is currently exploring the issue of allowing pharmacists to follow newer evidence-based information about drug storage, stability, compatibility, and beyond use dating found in recognized compendia or published research. Yet, our most recent ISMP Lifetime Achievement Award recipient (and compendia author) Lawrence A. Trissel, BS Pharm, FASHP, pointed out a problem with this otherwise promising safety effort: other than minimal pre-market testing by product manufacturers, fewer and fewer studies on drug storage, stability, compatibility, and beyond use dating are being conducted in the US. Trissel noted, “Over the last 20 or 25 years, this entire area of study and research has undergone a transformation in the US, withering into near non-existence.” Without ongoing studies, key product information that could promote safer pharmaceutical compounding, reduce medication errors, and lessen the impact of drug shortages is becoming quite scarce.

During his acceptance speech in December 2011 at the ISMP Cheers Awards gala, Trissel first shared his observation that the transformation of pharmacy education and practice into a clinical profession was crucial, and that we should all applaud the increased clinical roles that pharmacists are now playing, and the positive impact on patient safety that it can represent. But he went on to say that, in the rush to revolutionize the future of pharmacy, traditional pharmacy elements of value and need have been abandoned.

For one, he said, “New pharmacy graduates have been shortchanged regarding needed traditional skills in pharmaceutical mathematics, pharmaceutical compounding and preparation, and an adequate understanding of the basics of pharmaceutical chemistry and clinical pharmaceutics as well as with their application to direct patient care. From repeated episodes of pharmacy contamination of supposedly sterile preparations, to failure to recognize calcium phosphate precipitation in parenteral nutrition (PN) admixtures, to use of decomposed drugs, to failure to consider the impact of parenteral drug solution’s osmotic pressure, and all too many other cases, patients have repeatedly been injured and killed because of the inadequacy of this traditional drug knowledge in practice.”

Next, Trissel noted that the changes that were envisioned while moving pharmacy into a more clinical role were not intended to eliminate drug stability and compatibility research, but in the US, that has indeed been one outcome. He said, “Pharmacy students, including PharmD candidates, used to be frequent sources of new clinical pharmaceutics research, especially under the guidance of academic mentors. Unfortunately, few schools of pharmacy and their students conduct such laboratory research projects anymore.” In fact, Trissel reported that, at the December 2011 American Society of Health-System Pharmacists Midyear Clinical Meeting, the largest pharmacy meeting in the world, there were only three poster presentations on drug stability and compatibility. According to Trissel, virtually no support for this kind of laboratory research has come from the research foundations of major pharmacy organizations, even though the immediate applicability of the information to the clinical care setting is well recognized. “Apparently, drug stability and compatibility research has not been deemed sufficiently worthy of their support,” said Trissel.

If you doubt the impact that this de-emphasis of clinical pharmaceutics has had, consider the amount of new research studies published to support the clinical care of patients. In 1991 and 1992 there were 245 newly published clinical pharmaceutics research articles incorporated into the 7th edition of Trissel‘s Handbook on Injectable Drugs. Most of the studies came from US researchers in academia, pharmacy practice, and pharmacy students performing laboratory-based research. Twenty years later, Trissel noted that the upcoming 17th edition of the Handbook on Injectable Drugs (his last) will incorporate less than 45 new research articles, most from foreign researchers. In the last 20 years, there has been more than an 80% decline in new research studies of drug compatibility and stability.

Trissel believes clinical pharmaceutics research is viewed by much of the present day pharmacy profession as an activity outside of the profession. He said, “In past decades, things were very different. This kind of laboratory-based research was considered of value to patient care by the pharmacy profession. But now, the changes in pharmacy education and practice have led to the point that drug stability and compatibility research is just about dead. It is not as if the pharmacy profession in the US has ‘dropped the ball’; it is as if the team abandoned the field and walked away.”

Trissel concluded his acceptance speech by challenging the audience: “Whose job is it to protect patients from harm from drug instabilities and incompatibilities and other aspects of clinical pharmaceutics? Nurses and physicians? Not likely. Drug companies or the FDA? Even less likely. If not pharmacists, the self-declared drug experts, then who? If the pharmacy profession in the US abandons it, what does that say about pharmacy schools, pharmacy professional institutions and associations, and pharmacy practitioners?”

ISMP supports and honors Lawrence Trissel and his remarkable lifetime achievements in the field of drug stability and compatibility and, ultimately, patient safety. He has created the largest electronic clinical pharmaceutics database of its kind. We agree that drug stability and compatibility testing is important to patient care and safety, and that a way needs to be found for traditional concepts and skills, including clinical pharmaceutics, to be reintroduced and reemphasized in both pharmacy education and practice before these skills are lost. We worry about who will step up to the plate to fill the immense void at the end of Trissel’s long career. We hope the pharmacy community and others will help spark interest again in clinical pharmaceutics among pharmacy students and practitioners, and to promote graduate work in pharmaceutics to reinforce the importance and relevance of this research to clinical care needs and safety. And, as Trissel aptly noted, “This needs to be done while maintaining the gains in clinical skills and practice that have been won.”